Clinical Study Of Primary Hyperparathyroidism And Identification Of Novel Pathogenic Genes Of Primary Hyperparathyroidism Of CDC73 Mutation

Objective:This study aimed to retrospectively analyze the cases of primary hyperparathyroidism in our hospital over the past 12 years and to identify and study the mechanism of the novel CDC73 pathogenicity in sporadic primary hyperparathyroidism.Methods:1.Retrospective analysis of 12 years of primary hyperparathyroidism in our hospital,summarize the incidence,clinical symptoms,pathological types and other information.2.Collect peripheral blood and tissue samples of patients,using the second-generation sequencing identificate new CDC73 mutation sites.3.To construct the mutated site plasmid,the expression of the target protein was verified by West blot and RT-PCR,and the nuclear localization and protein expression of Leo1 and Paf1 were detected.Meanwhile,the related experiments on proliferation and apoptosis were carried out.Results:Data from a single clinical center shows the incidence of asymptomatic and symptomatic hyperparathyroidism is still on the rise in southeast China.The incidence of parathyroid cancer is low,but it obviously has an upward trend.A new CDC73 gene frameshift mutation(c.104 delA site sites)was identified.West blotting demonstrated a lower level of the Asn35 Met mutant parafibromin expression compared to the wild-type.Results of subcellular localization exhibited impaired nucleolar localization in Asn35 Met mutant.CDC73 mutation group Leo1,Paf1 expression decreased.The CDC73 mutation group lost the ability of inhibiting Cyclin D1 and c-myc,and the proportion of cell cycle G2 / M phase increased.Cell proliferation ability increased to a certain extent.Conclusion:The primary hyperparathyroidism is still symptomatical and the incidence has been on the rise over the past 12 years in southeast China.The novel CDC73 mutation causes the expression of parafibromin to decline and loses its nucleolus localization.At the same time,the disinhibition of Cyclin D1 and c-myc and the increase of G2 / M proportion in cell cycle lead to the enhancement of cell proliferation.